ABSTRACT Cigarette remains the leading cause of preventable death and poses an immense economic and health burden, in particular for those affected by comorbid anxiety and mood disorders. Cigarette smokers who suffer from elevated emotional distress smoke at greater rates, report greater dependence, and experience tremendous difficulty quitting. Negative reinforcement models of cigarette dependence suggest that transdiagnostic processes that promote avoidance and escape of affective distress contribute to the development and maintenance of smoking. Transdiagnostic vulnerabilities may also explain why individuals with depressive and anxiety symptoms (i.e., emotional distress) are particularly prone to smoking dependence and poor cessation outcomes. Novel smoking cessation interventions designed to target transdiagnostic vulnerabilities largely rely upon the development of cognitive-behavioral strategies. However, automatic visceral responses to emotional distress may impede the utilization of intentional self-control strategies. One notable gap in the development of integrated and behavioral treatments for cigarette smokers with elevations in emotional distress is directly addressing transdiagnostic physiological processes, such as cardiac vagal activity that underlie smoking and emotional disorder comorbidity. Cardiac vagal activity is critical in the effective modulation of physiological and emotional processes. Dysregulation in this system is observed across various forms of psychopathology and cigarette smoking, and associated with symptom severity and recovery. Heart rate variability biofeedback (HRVB) interventions offer a simple and effective means of promoting cardiac vagal tone and flexibility, but have not yet been applied to smokers with comorbid emotional disorder symptoms. Informed by this research, the current proposal seeks to fill an existing gap in the development of integrated transdiagnostic interventions for smokers with elevations in emotional distress by developing and pilot testing HRVB as a treatment adjunct for smoking cessation. We expect two significant outcomes from the proposed research. To determine whether an integrated HRVB and smoking cessation treatment (1) is feasible in smokers with co-occurring elevations in emotional distress; and (2) results in significantly greater smoking cessation outcomes as compared to a contact time matched sham breathing condition. We will also examine whether HRVB improves continuous smoking outcomes and emotional distress. Finally, we will explore distress tolerance, and cardiac vagal tone and flexibility, as treatment mechanisms. Via the development of a biobehavioral smoking cessation treatment, the proposal is expected to push the current status quo of novel smoking cessation intervention programs and have a significant positive impact on smokers with comorbid emotional psychopathology.